Date of Award

2019

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Scott E. Hensley

Abstract

The goal of vaccinology is to create robust and long-lasting protection against pathogen challenge. For influenza, while vaccination can result in nearly 50% efficacy, antibody responses rarely provide long-lived protection. While this is largely due to the rapid evolution of influenza and subsequent evasion of population immune responses, it has become increasingly clear that population variability in antibody repertoires further undermines current vaccine strategies. As such, understanding person-to-person differences is a critical part of creating protection strategies that are universally useful. Here, we study how antibody repertoires can be shaped by early life exposures to influenza. We show that primary exposure to influenza can shape the antibody repertoire generated upon vaccination later in life. We have previously demonstrated that the influenza antigens seen throughout life affect the total antibody repertoire and influence the specificity of the antibody response. Here, we investigate how these different types of antibody responses place selective pressure on in vitro evolution of influenza. We suggest that certain types of antibody repertoires have the capacity to direct novel viral variant selection in vivo. As we search for a more universal influenza vaccine, these studies will prove instrumental in creating more efficacious vaccine strategies. Additionally, they may be useful in understanding how antibody repertoires may predict future influenza evolution.

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Available to all on Monday, January 09, 2023

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Virology Commons

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